Display options
Cite
Manikowski D, Kastl P, Schürmann S, et al. C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation. Front Cell Dev Biol. 2021;8:615698doi: 10.3389/fcell.2020.615698.
Manikowski, D., Kastl, P., Schürmann, S., Ehring, K., Steffes, G., Jakobs, P., & Grobe, K. (2020). C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation. Frontiers in cell and developmental biology, 8615698. https://doi.org/10.3389/fcell.2020.615698
Manikowski, Dominique, et al. "C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation." Frontiers in cell and developmental biology vol. 8 (2020): 615698. doi: https://doi.org/10.3389/fcell.2020.615698
Manikowski D, Kastl P, Schürmann S, Ehring K, Steffes G, Jakobs P, Grobe K. C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation. Front Cell Dev Biol. 2021 Jan 12;8:615698. doi: 10.3389/fcell.2020.615698. eCollection 2020. PMID: 33511123; PMCID: PMC7835520.
Copy Download .nbib Format: NLM
Share it on

Front Cell Dev Biol. 2021 Jan 12;8:615698. doi: 10.3389/fcell.2020.615698. eCollection 2020.

C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation.

Frontiers in cell and developmental biology

Dominique Manikowski, Philipp Kastl, Sabine Schürmann, Kristina Ehring, Georg Steffes, Petra Jakobs, Kay Grobe

Affiliations

  1. Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.
  2. Institute of Neuro- and Behavioral Biology, University of Münster, Münster, Germany.

PMID: 33511123 PMCID: PMC7835520 DOI: 10.3389/fcell.2020.615698

Abstract

Hedgehog (Hh) morphogens are involved in embryonic development and stem cell biology and, if misregulated, can contribute to cancer. One important post-translational modification with profound impact on Hh biofunction is its C-terminal cholesteroylation during biosynthesis. The current hypothesis is that the cholesterol moiety is a decisive factor in Hh association with the outer plasma membrane leaflet of producing cells, cell-surface Hh multimerization, and its transport and signaling. Yet, it is not decided whether the cholesterol moiety is directly involved in all of these processes, because their functional interdependency raises the alternative possibility that the cholesterol initiates early processes directly and that these processes can then steer later stages of Hh signaling independent of the lipid. We generated variants of the C-terminal Hh peptide and observed that these cholesteroylated peptides variably impaired several post-translational processes in producing cells and Hh biofunction in

Copyright © 2021 Manikowski, Kastl, Schürmann, Ehring, Steffes, Jakobs and Grobe.

Keywords: Drosophila; Sonic hedgehog; hedgehog; morphogen; proteolysis; signaling

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Dev Cell. 2011 Jun 14;20(6):764-74 - PubMed
  2. Development. 2018 Sep 21;145(18): - PubMed
  3. Dev Biol. 2001 May 1;233(1):122-36 - PubMed
  4. Development. 2017 Sep 1;144(17):3134-3144 - PubMed
  5. Nat Commun. 2019 May 24;10(1):2320 - PubMed
  6. Sci Rep. 2014 Dec 08;4:7357 - PubMed
  7. Science. 2018 Aug 10;361(6402): - PubMed
  8. Mol Cell. 1999 Oct;4(4):633-9 - PubMed
  9. Biochem J. 2009 Jul 29;422(1):119-28 - PubMed
  10. Dev Biol. 2006 Jun 1;294(1):104-18 - PubMed
  11. Cell. 2001 Jun 1;105(5):599-612 - PubMed
  12. J Biol Chem. 2012 Dec 21;287(52):43708-19 - PubMed
  13. Genetics. 2006 Jun;173(2):769-77 - PubMed
  14. Trends Cell Biol. 2011 Apr;21(4):238-46 - PubMed
  15. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6548-53 - PubMed
  16. J Cell Sci. 2015 Jun 15;128(12):2374-85 - PubMed
  17. Curr Biol. 2005 Mar 8;15(5):480-8 - PubMed
  18. Dev Cell. 2003 Feb;4(2):191-204 - PubMed
  19. Science. 2007 Oct 5;318(5847):66-8 - PubMed
  20. Nature. 2018 Aug;560(7716):128-132 - PubMed
  21. Fly (Austin). 2014;8(1):36-42 - PubMed
  22. Biochem Biophys Res Commun. 1997 Aug 18;237(2):465-9 - PubMed
  23. J Cell Sci. 2014 Apr 15;127(Pt 8):1726-37 - PubMed
  24. J Biol Chem. 2007 Jun 8;282(23):16924-33 - PubMed
  25. Mol Biol Cell. 2015 Dec 15;26(25):4700-17 - PubMed
  26. Cell. 1996 Jul 12;86(1):21-34 - PubMed
  27. Nat Rev Genet. 2006 Nov;7(11):841-50 - PubMed
  28. J Cell Sci. 2017 Oct 1;130(19):3261-3271 - PubMed
  29. J Biol Chem. 1998 May 29;273(22):14037-45 - PubMed
  30. Cell Rep. 2012 Aug 30;2(2):308-20 - PubMed
  31. BMC Dev Biol. 2005 Sep 30;5:21 - PubMed
  32. Biochem J. 2011 Oct 15;439(2):185-93 - PubMed
  33. Development. 1997 Mar;124(6):1227-37 - PubMed
  34. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):912-7 - PubMed
  35. Elife. 2018 Mar 09;7: - PubMed
  36. Nature. 2001 Jun 7;411(6838):716-20 - PubMed
  37. Genes Dev. 2012 Jun 15;26(12):1312-25 - PubMed
  38. Sci Rep. 2016 May 20;6:26435 - PubMed
  39. Development. 2008 Mar;135(6):1097-106 - PubMed
  40. Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6394-9 - PubMed
  41. Genes Dev. 1992 Dec;6(12B):2635-45 - PubMed
  42. Development. 1995 Aug;121(8):2265-78 - PubMed
  43. Development. 2004 May;131(10):2395-408 - PubMed
  44. Cell. 2008 Jun 27;133(7):1214-27 - PubMed
  45. Nat Cell Biol. 2013 Nov;15(11):1269-81 - PubMed
  46. Biochemistry. 2001 Apr 10;40(14):4359-71 - PubMed
  47. Nature. 2005 May 5;435(7038):58-65 - PubMed
  48. Cell. 1999 Dec 23;99(7):803-15 - PubMed
  49. Nat Commun. 2017 Dec 7;8(1):1973 - PubMed
  50. Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12591-8 - PubMed
  51. Biochemistry. 2007 Apr 3;46(13):3933-41 - PubMed
  52. Development. 2006 Feb;133(3):471-83 - PubMed
  53. Development. 2006 Feb;133(3):407-18 - PubMed
  54. J Biol Chem. 2012 Jun 22;287(26):21950-6 - PubMed
  55. Development. 1993 Jun;118(2):401-15 - PubMed
  56. J Biol Chem. 2011 Jul 1;286(26):23608-19 - PubMed
  57. Elife. 2017 Aug 21;6: - PubMed
  58. Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7): - PubMed
  59. Development. 2002 May;129(9):2223-32 - PubMed
  60. Trends Genet. 2004 Oct;20(10):498-505 - PubMed
  61. Cell. 1993 Dec 3;75(5):927-38 - PubMed
  62. J Biol Chem. 1994 Oct 21;269(42):26280-5 - PubMed
  63. J Biol Chem. 2015 Feb 6;290(6):3293-307 - PubMed
  64. Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5866-E5875 - PubMed
  65. Development. 2007 Jun;134(11):2095-105 - PubMed
  66. Science. 1996 Oct 11;274(5285):255-9 - PubMed
  67. Development. 2004 Feb;131(3):601-11 - PubMed
  68. PLoS Biol. 2005 Mar;3(3):e66 - PubMed
  69. Nat Commun. 2014 Dec 04;5:5649 - PubMed
  70. Development. 1997 Nov;124(22):4697-705 - PubMed
  71. J Biol Chem. 2013 May 24;288(21):14756-68 - PubMed

Publication Types